Vasculitis: mechanisms involved and clinical manifestations

Abstract

Systemic vasculitis, an inflammatory necrotizing disease of the blood vessel walls, can occur secondary to autoimmune diseases, including connective tissue diseases. Various pathogenic mechanisms have been implicated in the induction of vasculitis, including cell-mediated inflammation, immune complex-mediated inflammation and autoantibody-mediated inflammation. This inflammatory activity is believed to contribute to accelerated atherosclerosis, and also leads to increased risk for cardiovascular events in patients with rheumatoid arthritis and systemic lupus erythematosus. Endothelial cell activation is a common pathogenic pathway in the systemic vasculitis associated with rheumatoid arthritis and systemic lupus erythematosus, with elevated levels of endothelin-1 potentially inducing vascular dysregulation.

Figure 1

Classification of the systemic vasculitis. Reproduced with permission from Jennette et al. Arthritis Rheum 1994 © John Wiley & Sons/American College of Rheumatology [2].

Figure 2

Pathogenesis of giant cell arteritis. (a) Recruitment and stimulation of antigen-specific T cells by dendritic cells. Interferon-γ regulates the differentiation and function of macrophages. Macrophages in the adventitial layer supply interleukin-1 and interleukin-6, and in the media secrete metalloproteinases. (b) Platelet-derived growth factor and vascular endothelial growth factor are responsible for intimal hyperplasia, then favour lumen-occlusive arteritis. Reproduced with permission from Weyland et al. N Engl J Med 2003 Copyright © 2003 Massachusetts Medical Society [5].

Figure 3

Data showing increased cardiovascular risk in patients with RA versus the normal population. MI, myocardial infarction; RA, rheumatoid arthritis. Reproduced with permission from Nicola et al. Arthritis Rheum 2005 and Maradit-Kremers et al. Arthritis Rheum 2005 © John Wiley & Sons/American College of Rheumatology [16,18].

Figure 4

Enhanced cardiovascular risk in SLE and SLE-related risk factors. HDL, high-density lipoprotein; LDL, low-density lipoprotein; SLE, systemic lupus erythematosus. Reproduced with permission from Nicola et al. N Engl J Med 2003 Copyright © 2003 Massachusetts Medical Society [18].

Figure 5

Pathways leading to nuclear factor-κB dependent endothelial cell activation. Ab, antibody; IC, immune complex; JNK, c-Jun amino-terminal kinase; LDL, low-density lipoprotein; MAPK, mitogen-activated protein kinase; MyD88, myeloid differentiation primary response gene 88; NF-κB, nuclear factor-κB; PAI, plasminogen activator inhibitor; ROS, reactive oxygen species; TLR, Toll-like receptor; TM, thrombomodulin; TR, thrombin receptor. Reprinted from Iba et al.: The role of the endothelium in changes in procoagulant activity in sepsis. J Am Coll Surg 1998; 187(3):321–329. © 1998 by the American College of Surgeons, with permission from Elsevier [36].

Figure 6

Comparison of maintenance therapy with cyclophosphamide (grey line) or azathioprine (black line) in ANCA-associated vasculitis. ANCA, anti-neutrophil cytoplasmic antibody. Reproduced with permission from Jayne et al. N Engl J Med 2003 © 2003 Massachusetts Medical Society [49].